Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis Journal Article


Authors: Thorek, D. L. J.; Watson, P. A.; Lee, S. G.; Ku, A. T.; Bournazos, S.; Braun, K.; Kim, K.; Sjostrom, K.; Doran, M. G.; Lamminmaki, U.; Santos, E.; Veach, D.; Turkekul, M.; Casey, E.; Lewis, J. S.; Abou, D. S.; Van Voss, M. R. H.; Scardino, P. T.; Strand, S. E.; Alpaugh, M. L.; Scher, H. I.; Lilja, H.; Larson, S. M.; Ulmert, D.
Article Title: Internalization of secreted antigen-targeted antibodies by the neonatal Fc receptor for precision imaging of the androgen receptor axis
Abstract: Targeting the androgen receptor (AR) pathway prolongs survival in patients with prostate cancer, but resistance rapidly develops. Understanding this resistance is confounded by a lack of noninvasive means to assess AR activity in vivo. We report intracellular accumulation of a secreted antigen-targeted antibody (SATA) that can be used to characterize disease, guide therapy, and monitor response. AR-regulated human kallikrein-related peptidase 2 (free hK2) is a prostate tissue-specific antigen produced in prostate cancer and androgen-stimulated breast cancer cells. Fluorescent and radio conjugates of 11B6, an antibody targeting free hK2, are internalized and noninvasively report AR pathway activity in metastatic and genetically engineered models of cancer development and treatment. Uptake is mediated by a mechanism involving the neonatal Fc receptor. Humanized 11B6, which has undergone toxicological tests in nonhuman primates, has the potential to improve patient management in these cancers. Furthermore, cellspecific SATA uptake may have a broader use for molecularly guided diagnosis and therapy in other cancers. © 2016 The Authors, some rights reserved.
Journal Title: Science Translational Medicine
Volume: 8
Issue: 367
ISSN: 1946-6234
Publisher: American Association for the Advancement of Science  
Date Published: 2016-11-30
Start Page: 367ra167
Language: English
DOI: 10.1126/scitranslmed.aaf2335
PROVIDER: scopus
PUBMED: 27903863
DOI/URL:
Notes: Article -- Export Date: 3 January 2017 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Peter T Scardino
    621 Scardino
  2. Darren Veach
    60 Veach
  3. Hans Gosta Lilja
    286 Lilja
  4. Elmer B Santos
    25 Santos
  5. Daniel Thorek
    20 Thorek
  6. Hans David Staffan Ulmert
    49 Ulmert
  7. Philip A Watson
    17 Watson
  8. Jason S Lewis
    242 Lewis
  9. Steven M Larson
    762 Larson
  10. Howard Scher
    816 Scher
  11. Emily Catherine Casey
    9 Casey
  12. Michael G. Doran
    17 Doran
  13. Anson Tai Ku
    4 Ku
  14. Kwanghee   Kim
    10 Kim
  15. Sang Gyu   Lee
    7 Lee